Memorial Sloan Kettering Cancer Center

About: Memorial Sloan Kettering Cancer Center is a healthcare organization based out in New York, New York, United States. It is known for research contribution in the topics: Cancer & Population. The organization has 30293 authors who have published 65381 publications receiving 4462534 citations. The organization is also known as: MSKCC & New York Cancer Hospital.

Mitochondrial import efficiency of ATFS-1 regulates mitochondrial UPR activation.

Abstract: To better understand the response to mitochondrial dysfunction, we examined the mechanism by which ATFS-1 (activating transcription factor associated with stress–1) senses mitochondrial stress and communicates with the nucleus during the mitochondrial unfolded protein response (UPRmt) in Caenorhabditis elegans. We found that the key point of regulation is the mitochondrial import efficiency of ATFS-1. In addition to a nuclear localization sequence, ATFS-1 has an N-terminal mitochondrial targeting sequence that is essential for UPRmt repression. Normally, ATFS-1 is imported into mitochondria and degraded. However, during mitochondrial stress, we found that import efficiency was reduced, allowing a percentage of ATFS-1 to accumulate in the cytosol and traffic to the nucleus. Our results show that cells monitor mitochondrial import efficiency via ATFS-1 to coordinate the level of mitochondrial dysfunction with the protective transcriptional response.

Intestinal Domination and the Risk of Bacteremia in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Abstract: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for a range of malignant and nonmalignant disorders. Pre-transplant conditioning transiently ablates circulating granulocytes and monocytes and markedly increases susceptibility to disseminated infections [1, 2]. Mucosal barrier injury is also a complication of allo-HSCT and enables commensal microbes to invade underlying tissues and the bloodstream [3]. As a result, systemic bacterial infections are frequent during the early transplant period [4–6]. Vancomycin-resistant Enterococcus (VRE), viridians-group Streptococcus, and aerobic gram-negative bacteria are the most common causes of bloodstream infection following allo-HSCT [5–8]. Why some patients develop bacteremia while others do not is unclear. The complex microbial populations colonizing the human intestine provide resistance to infection. The intestinal microbiota also serves as a sanctuary for highly antibiotic-resistant bacteria [9]. Prior studies using in vitro culture methods have characterized microbial populations inhabiting the intestine [10]; more recently, massively parallel pyrosequencing of bacterial 16S ribosomal RNA (rRNA) encoding genes has provided new insights into the composition and complexity of the intestinal microbiota by identifying bacterial taxons that are not readily cultivated in vitro [11–14]. These approaches have demonstrated the compositional changes and resilience of the intestinal microbiota of healthy individuals after antibiotic treatment [12]. Studies with mice demonstrated dramatic changes in the microbiota of the ileum and cecum following antibiotic treatment, and dramatic expansion of antibiotic-resistant microbes such as vancomycin-resistant Enterococcus (VRE) [15]. Intestinal expansion of VRE following antibiotic treatment is also seen in humans, with episodes of VRE domination in patients undergoing allo-HSCT preceding the development of VRE bacteremia in 2 patients [15]. Because the effect of allo-HSCT conditioning, prolonged neutropenia, and antibiotic administration on the gastrointestinal tract microbiota is unknown, we characterized the fecal microbiota of patients undergoing transplant at multiple time points using 454 pyrosequencing of 16S rRNA genes. (Data deposition: 454 pyrosequencing reads have been deposited in the National Center for Biotechnology Information Sequence Read Archive.)

Patterns of cervical lymph node metastasis from squamous carcinomas of the upper aerodigestive tract

Abstract: A consecutive series of 1,081 previously untreated patients undergoing 1,119 radical neck dissections (RNDs) for squamous carcinoma of the head and neck was reviewed to study the patterns of nodal metastases. Primary tumors were located in the oral cavity in 501 patients, in the oropharynx in 207 patients, in the hypopharynx in 126 patients, and in the larynx in 247 patients. Lymph node metastases were confirmed histologically in 82% of 776 therapeutic neck dissections, and micrometastases were discovered in 33% of 343 elective RNDs. Lymph node groups in the neck were described by levels (I to V). Predominance of certain levels was seen for each primary site. Levels I, II, and III were at highest risk for metastasis from cancer of the oral cavity, and levels II, III, and IV were at highest risk for metastasis from carcinomas of the orpharynx, hypopharynx, and larynx. Supramohyoid neck dissection (clearing levels I, II, and III) for NO patients with primary squamous cell carcinomas of the oral cavity and anterolateral neck dissection (clearing levels II, III, and IV) for NO patients with primary squamous cell carcinomas of the oropharynx, hypopharynx, and larynx are recommended.